Myocarditis frequently follows viral infections in both humans and experimental animals. However, growing evidence indicates cardiac injury results not from virus induced myolysis, but from T cell dependent immunopathogenic mechanisms. Male Balb/c mice infected with a myocarditic variant of coxsackievirus group B, type 3 (CVB3M) develop two distinct immune T cell populations involved in myocarditis. One recognizes antigens on uninfected myocytes (autoreactive cytolytic T lymphocyte, ACTL) and the other recognizes antigens on infected myocytes (virus specific cytolytic T lymphocyte, VSCTL). Evidence to date shows ACTL cause predominant myocardial injury in this mouse strain but ACTL sensitization in vivo depends upon a prior VSCTL response. VSCTL which belong to the 13T4+ (T helper) cell population, presumably produce lymphokines and induce either 1A expression on cardiocytes or infiltration of 1A+ inflammatory cells into the heart allowing myocyte antigen presentation to ACTL precursors. The goals of the present investigation are to characterize the antigens recognized by the two CTL populations and further elucidate the interactions of VSCTL and ACTL resulting in autoimmunity to heart antigens.